Of pyrrolizidine alkaloids

The combination of positive and negative charges within the same molecule causes a more complicated situation, which obviously has not been well-defined to date. A quite large number of pyrrolizidine alkaloids are related to Otonecine (8) (Scheme 3). Spectroscopic investigations show that these alkaloids exist in the nonionized form in CDCI3, and in the zwitterionic form in D2O (00JNP857, 71TL3421). The dipolar structure is the result of an intramolecular interaction between a nucleophilic and an electrophilic center. 

Hudlicky and coworkers also reported a related 2-pyrroline formation from viny-laziridines [81], which are extremely useful for the synthesis of pyrrolizidine alkaloids such as the protected (+)-trihydroxyheliotridane 210 (Scheme 2.51). Since the pyrolysis of either diastereomer of 208 furnished the cyclized product 209 as a... 

Hartmann T, Ober D (2000) Biosynthesis and Metabolism of Pyrrolizidine Alkaloids in Plants and Specialized Insect Herbivores. 209. 207-243 Haseley SR, Kamerling JP, Vliegenthart JFG (2002) Unravelling Carbohydrate Interactions with Biosensors Using Surface Plasmon Resonance (SPR) Detection. 218 93-114... 

Note It is reported that the use of chlorobenzene as solvent is essential when the reagent is to be used to detect aromatic amines [1]. In the case of steroids, penicillins, diuretics and alkaloids the reaction should be accelerated and intensified by spraying afterwards with dimethylsulfoxide (DMSO) or dimethylformamide (DMF), indeed this step makes it possible to detect some substances when this would not otherwise be possible [5,9-11] this latter treatment can, like heating, cause color changes [5,9]. Penicillins and diuretics only exhibit weak reactions if not treated afterwards with DMF [10, 11]. Steroids alone also yield colored derivatives with DMSO [9]. Tlreatment afterwards with diluted sulfuric acid (c = 2 mol/L) also leads to an improvement in detection sensitivity in the case of a range of alkaloids. In the case of pyrrolizidine alkaloids it is possible to use o-chloranil as an alternative detection reagent however, in this case it is recommended that the plate be treated afterwards with a solution of 2 g 4-(dimethyl-amino)-benzaldehyde and 2 ml boron trifluoride etherate in 100 ml anhydrous ethanol because otherwise the colors initially produced with o-chloranil rapidly fade [12]. 

Enantioenriched (-)-rosmarinecine, which belongs to the group of pyrrolizidine alkaloids [413], has been synthesized by Goti, Brandi and coworkers applying an intramolecular 1,3-dipolar cycloaddition as the key step [414]. The required nitrone was obtained in situ from L-malic acid. Moreover, 1,3-dienes as precursors for a cy-... 

The synthesis of pyrrolizidine alkaloid (-)-rosmarinecine illustrates the power of the fused mode tandem cycloaddition, as shown in Scheme 8.40.180 The all-cA relationship at the three contiguous centers C(l), C(7), and C(7a) can be constructed in a single-pot reaction with correct stereochemistry but C(6) cannot. 

Macel G L, Klinkhamer P, Vrieling K and van der Meijden E (2002), Diversity of pyrrolizidine alkaloids in Senecio species does not affect the specialist herbivore Tyria jacobaeae , Oecologia, 133, 541-550. 

Highly selective 1,3-dipolar cycloaddition reactions of nitrone (154) with acrylates have been used in the total syntheses of pyrrolizidine alkaloids, 7-deoxy-casuarine (572) and hyacinthacine A2 (573) (Scheme 2.263) (772). 

Extensive metabolic work continues with the pyrrolizidine alkaloids many of which are known toxic principles of plants responsible for conditions such as irreversible hemorrhagic liver necrosis, megalocytosis, and cancer. Considerable interest remains in the metabolism of pyrrolizidine alkaloids and their A-oxides to metabolic pyrroles thought to participate in molecular events associated with the above-mentioned toxicities. The chemistry and pharmacological properties of the pyrrolizidine alkaloids is authoritatively discussed by Wrobel in Volume 26 of this treatise. 

Selective ring closure of cyclic secondary alkyl radicals onto the central carbon atom of allenes have been investigated in the course of pyrrolizidine alkaloid syntheses [69]. Thus, reduction of the phenylselenyl-substituted N-(l,2-buten-4-yl)pyrroli-done 42 with Bu3SnH via a radical chain mechanism provides 51% of target compound 44 as a 78 22 mixture of diastereomers (Scheme 11.14). The stereoselectivity... 

Scheme 11.14 The synthesis of building block 44 in the total synthesis of (+)-heliotridine, a necine base present in a large diversity of pyrrolizidine alkaloids [69], a)78 22 mixture of diastereomers.

Figure 2.12 Metabolic activation by the liver of pyrrolizidine alkaloid to the toxic pyrrole (liver bound and highly toxic) and the glutathione conjugate (excretion metabolite).

Edgar, J.A. and Smith, L.W. (2000). Transfer of pyrrolizidine alkaloids into eggs Food safety implications, in Tu, A.T. and Gaffield W., Eds., Natural and selected synthetic toxins biological implications, American Chemical Society, Washington, pp. 118-128. 

Hartmann, T. 1999. Chemical ecology of pyrrolizidine alkaloids. Planta, 207 483-495. 

Pelser, P. B., Vos de, H., Theuring, C Beuerle, T., Vrieling, K. and Hartmann, T. 2005. Erequent gain and loss of pyrrolizidine alkaloids in the evolution of Senecio section Jacobaea (Asteraceae). Phytochemistry, 66 1285-1295. 

Dobler, S., Haberer, W., Witte, L. and Hartmann, T. 2000. Selective sequestration of pyrrolizidine alkaloids from diverse host plants by Longitarsus flea beetles (Coleoptera, Chrysomelidae). Journal of Chemical Ecology, 26 1281-1298. 

Culvenor, C. C. J. 1983. Estimated intakes of pyrrolizidine alkaloids by humans. A eomparison with dose rates eausing tumors in rats. Journal of Toxicology and Environmental Health, 11 625-635. 

Biek, Y. A. E., Culvenor, C. C. J. and Jago, M. V. 1975. Comparative effects of pyrrolizidine alkaloids and related eompounds on leukocyte cultures from Potorus triadactylus. Cytobios, 14 151-160. 

Mattocks, A. R. 1986. Chemistry and Toxicology of Pyrrolizidine Alkaloids. London - New York Aeademie Press. 

Butler, W. H., Mattoeks, A. R. and Barnes, J. M. 1970. Lesions in the liver and lungs of rats given pyrrole derivatives of pyrrolizidine alkaloids. Journal of Pathology, 100 169-175. 

Knight, A. P., Kimberling, C. V., Stermitz, E. R. and Roby, M. R. 1984. Cynoglossum officinale (Hound s tongue) - A case of pyrrolizidine alkaloid poisoning in horses. Journal of American Veterinary Medicine Association, 185 647-650. 

Hartmann, T. and Toppel. G. 1987. Senecionine A-oxide, the primary product of pyrrolizidine alkaloid biosynthesis in root cultures of Senecio vulgaris. Phytochemistry, 26 1639-1643. 

A diagram of the accumulation of pyrrolizidine alkaloids in some insect species during various developmental stages. 

More recently, Naidu and West have utilized a ring expansion reaction of spiro azetidinium ylide 167 in the synthesis of pyrrolizidine alkaloids. Spiro azetidinium ylide 167 is generated through a Cu(acac)2-catalyzed intramolecular reaction of a copper carbene complex with a pendant amino moiety. Subsequent [l,2]-shift gives fused bicyclic products 168 and 169 as a diastereomeric mixture. Each diastereomer was further converted to naturally occurring pyrrolizidines ( )-turneforcidine and ( )-platynecine, respectively (Scheme 18). ... 

---